Dataset Information

The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism.

ABSTRACT: Metabolism encompasses the biochemical processes that allow healthy cells to keep energy, redox balance and building blocks required for cell development, survival, and proliferation steady. Malignant cells are well-documented to reprogram their metabolism and energy production networks to support rapid proliferation and survival in harsh conditions via mutations in oncogenes and inactivation of tumor suppressor genes. Despite the histologic and genetic heterogeneity of tumors, a common set of metabolic pathways sustain the high proliferation rates observed in cancer cells. This review with a focus on lung cancer covers several fundamental principles of the disturbed glucose metabolism, such as the "Warburg" effect, the importance of the glycolysis and its branching pathways, the unanticipated gluconeogenesis and mitochondrial metabolism. Furthermore, we highlight our current understanding of the disturbed glucose metabolism and how this might result in the development of new treatments.

SUBMITTER: Vanhove K

PROVIDER: S-EPMC6873590 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism.

Vanhove Karolien K Graulus Geert-Jan GJ Mesotten Liesbet L Thomeer Michiel M Derveaux Elien E Noben Jean-Paul JP Guedens Wanda W Adriaensens Peter P

Frontiers in oncology 20191115

Metabolism encompasses the biochemical processes that allow healthy cells to keep energy, redox balance and building blocks required for cell development, survival, and proliferation steady. Malignant cells are well-documented to reprogram their metabolism and energy production networks to support rapid proliferation and survival in harsh conditions via mutations in oncogenes and inactivation of tumor suppressor genes. Despite the histologic and genetic heterogeneity of tumors, a common set of m ...[more]

PMID: 31803611

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Project description:BackgroundLocal tumor microenvironment (TME) plays a crucial role in immunotherapy for breast cancer (BC). Whereas, the molecular mechanism responsible for the crosstalk between BC cells and surrounding immune cells remains unclear. The present study aimed to determine the interplay between GPR81-mediated glucometabolic reprogramming of BC and the immune landscape in TME.Materials and methodsImmunohistochemistry (IHC) assay was first performed to evaluate the association between GPR81 and the immune landscape. Then, several stable BC cell lines with down-regulated GPR81 expression were established to directly identify the role of GPR81 in glucometabolic reprogramming, and western blotting assay was used to detect the underlying molecular mechanism. Finally, a transwell co-culture system confirmed the crosstalk between glucometabolic regulation mediated by GPR81 in BC and induced immune attenuation.ResultsIHC analysis demonstrated that the representation of infiltrating CD8+ T cells and FOXP3+ T cells were dramatically higher in BC with a triple negative (TN) subtype in comparison with that with a non-TN subtype (P < 0.001). Additionally, the ratio of infiltrating CD8+ to FOXP3+ T cells was significantly negatively associated with GPR81 expression in BC with a TN subtype (P < 0.001). Furthermore, GPR81 was found to be substantially correlated with the glycolytic capability (P < 0.001) of BC cells depending on a Hippo-YAP signaling pathway (P < 0.001). In the transwell co-culture system, GPR81-mediated reprogramming of glucose metabolism in BC significantly contributed to a decreased proportion of CD8+ T (P < 0.001) and an increased percentage of FOXP3+ T (P < 0.001) in the co-cultured lymphocytes.ConclusionGlucometabolic reprogramming through a GPR81-mediated Hippo-YAP signaling pathway was responsible for the distinct immune landscape in BC. GPR81 was a potential biomarker to stratify patients before immunotherapy to improve BC's clinical prospect.

Dataset Information

The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism.

Publications

The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism.

Similar Datasets

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